The present invention relates to a blood processing apparatus and a method for introducing blood into the blood processing apparatus. More particularly, the present invention relates to a blood processing apparatus comprising a chamber for introducing a metered quantity of a blood sample, so as to conduct various operations with respect to the blood such as analysis of blood components, e.g., electrochemical analysis of protein components contained in blood plasma, or blood cells—blood plasma separation. The present invention also relates to a method for introducing a blood sample into the chamber of such blood processing apparatus.
A variety of health diagnostic chips have recently been developed. Practically all the health diagnostic chips are card-type devices having a micro fluid passage structure called a MICROTAS (μ-TAS: Micro Total Analysis System). The transition to micro fluid passages is very useful because microscopic amounts of samples can be extracted from a living body. Furthermore, if the entire apparatus comprising a health diagnostic chip is miniaturized by employing microscopic fluid passages, the apparatus can be used not only in comparatively large hospitals, but also for POCT (Point Of Care Test: field diagnostics thereof) applications for conducting diagnostics in medical offices and at home.
The analysis object in the devices of this type is usually blood. Blood is a viscous liquid comprising blood cell, which are a particulate component, and blood plasma, which is a liquid component. Because a viscous blood sample is difficult to introduce into a micro fluid passage, a variety of attempts have been made to introduce the blood into micro fluid passages.
FIG. 20 shows a biosensor for electrochemically measuring a blood sugar value in a blood disclosed in Japanese Patent Application Laid-open No. 2000-065778. This biosensor has a structure in which a spacer 102 is sandwiched between two platforms 101, 103. A slit 104 for introducing blood that is formed in the spacer 102 is hydrophilized. Measurement electrodes 106, 107, 108 are disposed in the vicinity of an entry port 104a of the slit 104. Furthermore, an air port 105 is provided in the vicinity of a closed end 104b of the slit 104. The entry port 104a, electrodes 106 to 108, and air port 105 are arranged in a row in the order of description along the extension direction of the slit 104.
The blood sample introduced from the entry port 104a flows toward the electrodes 106 to 108 due to a capillary phenomenon inside the hydrophilized slit 104. Because the air present inside the slit 104 escapes to the side opposite that of the entry port 104 and is drained from the air port 105, the slit 104 can be filled with the blood sample up to the closed end 104b of the slit. Therefore, air bubbles do not remain (air bite does not occur) in the zone of the slit 104 corresponding to the electrodes 106 to 108. Furthermore, the volume of the blood sample introduced into the slit 104 can be quantitatively estimated. For those two reasons the electric signal obtained with the electrodes 106 to 108 has good reproducibility, and the quantity of sugar contained in the blood can be quantitatively determined. The structure in which the air port 104a is provided in the slit 104 is very important for introducing microquantities of solution into a microslit or micro fluid passage with a microliter volume of at least one representative length of several hundreds of micrometers to several millimeters.
In the biosensor shown in FIG. 20, because the electrodes 106 to 108 are positioned above the slit 104, it is not necessary to deliver the blood sample. However, certain measurements require the blood to be delivered or pretreated. For example, when CRP (C reactive proteins) contained in blood are measured electrochemically, blood cells are an inhibiting factor for measurements. Therefore, blood cells—blood plasma separation has to be carried out and the separated blood plasma component solution has to be measured. A method using a centrifugal force is one of the liquid delivery methods suitable for POCT applications.
The biosensor disclosed in Japanese Patent Application Tokuhyo No. 2001-503854 uses a centrifugal force generated by rotating a platform as a drive source for liquid delivery, and a solution can be delivered from one chamber to another chamber via a micro fluid passage. The delivery is based on the following principle. When the platform is not rotated, the liquid is held inside the chamber by surface tension generated on the interface of the chamber and micro fluid passage, but a centrifugal force generated by the rotation of the substrate disrupts the balance of forces and delivers the liquid to the other chamber. With this liquid delivery method, by contrast with the delivery using a pump, connecting a tube is not necessary. Therefore, a dead volume required to move the liquid is not produced. Furthermore, if a large number of fluid passages are provided in the platform, then a plurality of liquid delivery operations can be executed in parallel. Moreover, the above-described blood cell-blood plasma separation also can be realized with a centrifugal force. More specifically, because of a difference in density between the blood cells, which are a particulate component, and blood plasma, which is a liquid component, they can be separated from each other by a centrifugal force. Therefore, the liquid delivery method using a centrifugal force as a drive source, which is disclosed in Japanese Patent Application Tokuhyo No. 2001-503854, can be unified with blood cell-blood plasma separation. More specifically, both the blood cell-blood plasma separation in one chamber and the delivery of the separated blood plasma component solution into another chamber via a micro fluid passage can be realized by a centrifugal force. Japanese Patent Application Tokuhyo No. 2002-503331 and Japanese Patents No. 3356784 and 3469585 disclose liquid delivery methods using a centrifugal force.
However, the following problem is associated with air draining during blood sample introduction when a centrifugal force is used for blood cell-blood plasma separation and delivery.
Referring to FIG. 21, when no air port (see reference numeral 105 in FIG. 20) is provided in the chamber 200 for introducing the blood sample and a micro fluid passage 201 for delivery into another chamber (not shown in the figure) is caused to function as an air port, a limitation is placed on the position where the micro fluid passage 201 can be connected to the chamber 200. First, because the centrifugal force generated during rotation of the platform 202 acts in the direction of withdrawing from the rotary shaft 203, as shown by an arrow, an injection port 204 for injecting the blood sample into the chamber 200 has to be provided on the inner peripheral side (centripetal direction) of the chamber 200 in order to prevent the blood sample from scattering by a centrifugal force. The micro fluid passage 201 functioning as an air port has to be connected to the chamber 200 in a site 200a on the side opposite that of the injection port 204, that is, on the outer peripheral side. However, if blood plasma 205 and blood cells 206 are separated by a centrifugal force, then blood cells 206 contained in an amount of approximately 40-50% in the blood sample remain in the site 200a on the outermost peripheral side of the chamber 200a and the open section of the micro fluid passage 201 leading to the chamber 200 is clogged, thereby making the delivery impossible. If the connection position of the micro fluid passage 201 to the microchamber 200 is set from the inner periphery, as shown in FIG. 22, in order to avoid this clogging with the blood cells 206, then the air present in the microchamber 200 cannot be completely drained from the micro fluid passage 201 when the blood sample is introduced from the injection port 204, air bubbles 208 remain in the site 200a located on the outermost peripheral side of the microchamber 200, and air bite occurs, and metered introduction of the blood sample becomes impossible.
For the reasons described above, an air port has to be provided on the side of the chamber that is opposite the injection port, separately from the micro fluid passage, in order to drain reliably the air present in the chamber and to introduce metered quantities of the blood sample. However, in a structure where openings are provided at both ends of the chamber, that is when an injection port and air port are provided, the blood sample is scattered from one of the openings by a centrifugal force. As a result, an operation of sealing at least any one of the openings after the blood sample has been introduced is required. For example, an operation of pasting a sheet piece having adhesive capability surpassing the centrifugal force is required.